Skip to main content
Top
Published in: Clinical Orthopaedics and Related Research® 11/2011

01-11-2011 | Symposium: Bone Repair and Regeneration

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Authors: Manav Mehta, PhD, Georg N. Duda, PhD, Carsten Perka, MD, Patrick Strube, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 11/2011

Login to get access

Abstract

Background

Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear.

Questions/purposes

In a pilot study we determined the combined influence of gender and fixation stability on the callus of middle-aged rats regarding (1) biomechanical properties; (2) bridging over time; (3) callus formation; and (4) callus size, geometry, mineralization, and microstructure.

Methods

We osteotomized the left femur of 32 Sprague-Dawley rats (12 months old). Femurs were externally fixed with a gap of 1.5 mm in four groups of eight animals each: female semirigid, male semirigid, female rigid, and male rigid. Qualitative and quantitative in vivo radiographic analyses were performed twice weekly. Six weeks postoperatively, harvested femora were evaluated using micro-CT and biomechanical testing.

Results

Torsional stiffness and maximum torque at failure were higher in male and in semirigidly fixed fractures. Radiographic analysis revealed earlier bridging and callus formation in both male groups. Micro-CT analysis showed a larger callus size, altered geometry, and microstructure in males and semirigidly fixed animals, whereas mineralization was similar in all animals.

Conclusion

Our data suggest female gender represents an independent risk factor for bone healing in middle-aged rats. Although healing in females was delayed compared with males, they exhibited a similar response (superior callus properties) to a more semirigid fixation.

Clinical Relevance

While female gender appears to reflect a risk for impaired bone healing in middle-aged female rats, clinical studies would be required to confirm the finding in humans.
Literature
1.
go back to reference Carter DR, Beaupre GS, Giori NJ, Helms JA. Mechanobiology of skeletal regeneration. Clin Orthop Relat Res. 1998;355(Suppl):S41–55.PubMedCrossRef Carter DR, Beaupre GS, Giori NJ, Helms JA. Mechanobiology of skeletal regeneration. Clin Orthop Relat Res. 1998;355(Suppl):S41–55.PubMedCrossRef
2.
go back to reference Chang MA, Bishop AT, Moran SL, Shin AY. The outcomes and complications of 1,2-intercompartmental supraretinacular artery pedicled vascularized bone grafting of scaphoid nonunions. J Hand Surg [Am]. 2006;31:387–396.CrossRef Chang MA, Bishop AT, Moran SL, Shin AY. The outcomes and complications of 1,2-intercompartmental supraretinacular artery pedicled vascularized bone grafting of scaphoid nonunions. J Hand Surg [Am]. 2006;31:387–396.CrossRef
3.
go back to reference Claes LE, Heigele CA, Neidlinger-Wilke C, Kaspar D, Seidl W, Margevicius KJ, Augat P. Effects of mechanical factors on the fracture healing process. Clin Orthop Relat Res. 1998;355(Suppl):S132–147.PubMedCrossRef Claes LE, Heigele CA, Neidlinger-Wilke C, Kaspar D, Seidl W, Margevicius KJ, Augat P. Effects of mechanical factors on the fracture healing process. Clin Orthop Relat Res. 1998;355(Suppl):S132–147.PubMedCrossRef
4.
go back to reference Currey J. Measurement of the mechanical properties of bone: a recent history. Clin Orthop Relat Res. 2009;467:1948–1954.PubMedCrossRef Currey J. Measurement of the mechanical properties of bone: a recent history. Clin Orthop Relat Res. 2009;467:1948–1954.PubMedCrossRef
5.
go back to reference David V, Lafage-Proust MH, Laroche N, Christian A, Ruegsegger P, Vico L. Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences. Am J Physiol Endocrinol Metab. 2006;290:E440–447.PubMedCrossRef David V, Lafage-Proust MH, Laroche N, Christian A, Ruegsegger P, Vico L. Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences. Am J Physiol Endocrinol Metab. 2006;290:E440–447.PubMedCrossRef
6.
go back to reference Goodship AE, Kenwright J. The influence of induced micromovement upon the healing of experimental tibial fractures. J Bone Joint Surg Br. 1985;67:650–655.PubMed Goodship AE, Kenwright J. The influence of induced micromovement upon the healing of experimental tibial fractures. J Bone Joint Surg Br. 1985;67:650–655.PubMed
7.
go back to reference Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger TO. Fracture healing in the elderly patient. Exp Gerontol. 2006;41:1080–1093.PubMedCrossRef Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger TO. Fracture healing in the elderly patient. Exp Gerontol. 2006;41:1080–1093.PubMedCrossRef
8.
go back to reference Haas NP. Callus modulation—fiction or reality? [in German]. Der Chirurg Zeitschrift für alle Gebiete der operativen Medizin. 2000;71:987–988. Haas NP. Callus modulation—fiction or reality? [in German]. Der Chirurg Zeitschrift für alle Gebiete der operativen Medizin. 2000;71:987–988.
9.
go back to reference Kaspar K, Schell H, Toben D, Matziolis G, Bail HJ. An easily reproducible and biomechanically standardized model to investigate bone healing in rats, using external fixation. Biomed Tech (Berl). 2007;52:383–390.CrossRef Kaspar K, Schell H, Toben D, Matziolis G, Bail HJ. An easily reproducible and biomechanically standardized model to investigate bone healing in rats, using external fixation. Biomed Tech (Berl). 2007;52:383–390.CrossRef
10.
go back to reference Kraus KH, Kadiyala S, Wotton H, Kurth A, Shea M, Hannan M, Hayes WC, Kirker-Head CA, Bruder S. Critically sized osteo-periosteal femoral defects: a dog model. J Invest Surg. 1999;12:115–124.PubMedCrossRef Kraus KH, Kadiyala S, Wotton H, Kurth A, Shea M, Hannan M, Hayes WC, Kirker-Head CA, Bruder S. Critically sized osteo-periosteal femoral defects: a dog model. J Invest Surg. 1999;12:115–124.PubMedCrossRef
11.
go back to reference Li Z, Zhang W, Li ZB, Li JR. Abnormal union of mandibular fractures: a review of 84 cases. J Oral Maxillofac Surg. 2006;64:1225–1231.PubMedCrossRef Li Z, Zhang W, Li ZB, Li JR. Abnormal union of mandibular fractures: a review of 84 cases. J Oral Maxillofac Surg. 2006;64:1225–1231.PubMedCrossRef
12.
go back to reference Lienau J, Schell H, Duda GN, Seebeck P, Muchow S, Bail HJ. Initial vascularization and tissue differentiation are influenced by fixation stability. J Orthop Res. 2005;23:639–645.PubMedCrossRef Lienau J, Schell H, Duda GN, Seebeck P, Muchow S, Bail HJ. Initial vascularization and tissue differentiation are influenced by fixation stability. J Orthop Res. 2005;23:639–645.PubMedCrossRef
13.
go back to reference Mehta M, Strube P, Peters A, Perka C, Hutmacher D, Fratzl P, Duda GN. Influences of age and mechanical stability on volume, microstructure, and mineralization of fracture callus during bone healing: is osteoclast activity the key to age-related impaired healing? Bone. 2010;47:219–228.PubMedCrossRef Mehta M, Strube P, Peters A, Perka C, Hutmacher D, Fratzl P, Duda GN. Influences of age and mechanical stability on volume, microstructure, and mineralization of fracture callus during bone healing: is osteoclast activity the key to age-related impaired healing? Bone. 2010;47:219–228.PubMedCrossRef
14.
go back to reference Meyer MH, Meyer RA Jr. Genes with greater up-regulation in the fracture callus of older rats with delayed healing. J Orthop Res. 2007;25:488–494.PubMedCrossRef Meyer MH, Meyer RA Jr. Genes with greater up-regulation in the fracture callus of older rats with delayed healing. J Orthop Res. 2007;25:488–494.PubMedCrossRef
15.
go back to reference Mora G, Forriol F. Mechanical analysis of the healing of different osteotomies fixed externally. Int Orthop. 2000;24:295–298.PubMedCrossRef Mora G, Forriol F. Mechanical analysis of the healing of different osteotomies fixed externally. Int Orthop. 2000;24:295–298.PubMedCrossRef
16.
go back to reference Parker MJ, Raghavan R, Gurusamy K. Incidence of fracture-healing complications after femoral neck fractures. Clin Orthop Relat Res. 2007;458:175–179.PubMed Parker MJ, Raghavan R, Gurusamy K. Incidence of fracture-healing complications after femoral neck fractures. Clin Orthop Relat Res. 2007;458:175–179.PubMed
17.
go back to reference Perren SM. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. J Bone Joint Surg Br. 2002;84:1093–1110.PubMedCrossRef Perren SM. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. J Bone Joint Surg Br. 2002;84:1093–1110.PubMedCrossRef
18.
go back to reference Rubin CT, Bain SD, McLeod KJ. Suppression of the osteogenic response in the aging skeleton. Calcif Tissue Int. 1992;50:306–313.PubMedCrossRef Rubin CT, Bain SD, McLeod KJ. Suppression of the osteogenic response in the aging skeleton. Calcif Tissue Int. 1992;50:306–313.PubMedCrossRef
19.
go back to reference Schell H, Epari DR, Kassi JP, Bragulla H, Bail HJ, Duda GN. The course of bone healing is influenced by the initial shear fixation stability. J Orthop Res. 2005;23:1022–1028.PubMedCrossRef Schell H, Epari DR, Kassi JP, Bragulla H, Bail HJ, Duda GN. The course of bone healing is influenced by the initial shear fixation stability. J Orthop Res. 2005;23:1022–1028.PubMedCrossRef
20.
go back to reference Schmidmaier G, Wildemann B, Melis B, Krummrey G, Einhorn TA, Haas NP, Raschke M. Development and characterization of a standard closed tibial fracture model in the rat. Eur J Trauma. 2004;30:35–42.CrossRef Schmidmaier G, Wildemann B, Melis B, Krummrey G, Einhorn TA, Haas NP, Raschke M. Development and characterization of a standard closed tibial fracture model in the rat. Eur J Trauma. 2004;30:35–42.CrossRef
21.
go back to reference Sprague S, Bhandari M. An economic evaluation of early versus delayed operative treatment in patients with closed tibial shaft fractures. Arch Orthop Trauma Surg. 2002;122:315–323.PubMed Sprague S, Bhandari M. An economic evaluation of early versus delayed operative treatment in patients with closed tibial shaft fractures. Arch Orthop Trauma Surg. 2002;122:315–323.PubMed
22.
go back to reference Strube P, Mehta M, Baerenwaldt A, Trippens J, Wilson CJ, Ode A, Perka C, Duda G, Kasper G. Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity. Bone. 2009;45:1065–1072.PubMedCrossRef Strube P, Mehta M, Baerenwaldt A, Trippens J, Wilson CJ, Ode A, Perka C, Duda G, Kasper G. Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity. Bone. 2009;45:1065–1072.PubMedCrossRef
23.
go back to reference Strube P, Mehta M, Putzier M, Matziolis G, Perka C, Duda GN. A new device to control mechanical environment in bone defect healing in rats. J Biomech. 2008;41:2696–2702.PubMedCrossRef Strube P, Mehta M, Putzier M, Matziolis G, Perka C, Duda GN. A new device to control mechanical environment in bone defect healing in rats. J Biomech. 2008;41:2696–2702.PubMedCrossRef
24.
go back to reference Strube P, Sentuerk U, Riha T, Kaspar K, Mueller M, Kasper G, Matziolis G, Duda GN, Perka C. Influence of age and mechanical stability on bone defect healing: age reverses mechanical effects. Bone. 2008;42:758–764.PubMedCrossRef Strube P, Sentuerk U, Riha T, Kaspar K, Mueller M, Kasper G, Matziolis G, Duda GN, Perka C. Influence of age and mechanical stability on bone defect healing: age reverses mechanical effects. Bone. 2008;42:758–764.PubMedCrossRef
25.
go back to reference Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. 1995;10:1544–1549.PubMedCrossRef Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. 1995;10:1544–1549.PubMedCrossRef
26.
go back to reference White AA 3rd, Panjabi MM, Southwick WO. The four biomechanical stages of fracture repair. J Bone Joint Surg Am. 1977;59:188–192.PubMed White AA 3rd, Panjabi MM, Southwick WO. The four biomechanical stages of fracture repair. J Bone Joint Surg Am. 1977;59:188–192.PubMed
27.
go back to reference Yamagishi M, Yoshimura Y. The biomechanics of fracture healing. J Bone Joint Surg Am. 1955;37:1035–1068.PubMed Yamagishi M, Yoshimura Y. The biomechanics of fracture healing. J Bone Joint Surg Am. 1955;37:1035–1068.PubMed
28.
go back to reference Zlowodzki M, Obremskey WT, Thomison JB, Kregor PJ. Functional outcome after treatment of lower-extremity nonunions. J Trauma. 2005;58:312–317.PubMedCrossRef Zlowodzki M, Obremskey WT, Thomison JB, Kregor PJ. Functional outcome after treatment of lower-extremity nonunions. J Trauma. 2005;58:312–317.PubMedCrossRef
Metadata
Title
Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study
Authors
Manav Mehta, PhD
Georg N. Duda, PhD
Carsten Perka, MD
Patrick Strube, MD
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 11/2011
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-011-1914-y

Other articles of this Issue 11/2011

Clinical Orthopaedics and Related Research® 11/2011 Go to the issue

Symposium: Papers Presented at the 2010 Meeting of the Musculoskeletal Infection Society

Definition of Periprosthetic Joint Infection: Is There a Consensus?

Symposium: Papers Presented at the 2010 Meeting of the Musculoskeletal Infection Society

An Articulating Antibiotic Spacer Controls Infection and Improves Pain and Function in a Degenerative Septic Hip

Symposium: Papers Presented at the 2010 Meeting of the Musculoskeletal Infection Society

Infection Control Rate of Irrigation and Débridement for Periprosthetic Joint Infection

Symposium: Bone Repair and Regeneration

How Much Vitamin D Do We Need for Skeletal Health?